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Abstract In 2023, wildfires burned 15 million hectares in Canada, more than doubling the previous record. These wildfires caused a record number of evacuations, unprecedented air quality impacts across Canada and the northeastern United States, and substantial strain on fire management resources. Using climate models, we show that human-induced climate change significantly increased the likelihood of area burned at least as large as in 2023 across most of Canada, with more than two-fold increases in the east and southwest. The long fire season was more than five times as likely and the large areas across Canada experiencing synchronous extreme fire weather were also much more likely due to human influence on the climate. Simulated emissions from the 2023 wildfire season were eight times their 1985-2022 mean. With continued warming, the likelihood of extreme fire seasons is projected to increase further in the future, driving additional impacts on health, society, and ecosystems.

Abstract Northern forests are an important carbon sink, but our understanding of the driving factors is limited due to discrepancies between dynamic global vegetation models (DGVMs) and atmospheric inversions. We show that DGVMs simulate a 50% lower sink (1.1 ± 0.5 PgC yr−1 over 2001–2021) across North America, Europe, Russia, and China compared to atmospheric inversions (2.2 ± 0.6 PgC yr−1). We explain why DGVMs underestimate the carbon sink by considering how they represent disturbance processes, specifically the overestimation of fire emissions, and the lack of robust forest demography resulting in lower forest regrowth rates than observed. We reconcile net sink estimates by using alternative disturbance-related fluxes. We estimate carbon uptake through forest regrowth by combining satellite-derived forest age and biomass maps. We calculate a regrowth flux of 1.1 ± 0.1 PgC yr−1, and combine this with satellite-derived estimates of fire emissions (0.4 ± 0.1 PgC yr−1), land-use change emissions from bookkeeping models (0.9 ± 0.2 PgC yr−1), and the DGVM-estimated sink from CO2 fertilisation, nitrogen deposition, and climate change (2.2 ± 0.9 PgC yr−1). The resulting ‘bottom-up’ net flux of 2.1 ± 0.9 PgC yr−1 agrees with atmospheric inversions. The reconciliation holds at regional scales, increasing confidence in our results.

In the present study, MnO2 nanoparticles were synthesized using Citrus limetta peels extract and functionalized by chitosan polymer. Surface morphology analysis of chitosan functionalized MnO2 nanoparticles was carried out using a scanning electron microscope (SEM) and transmission electron microscope (TEM), which revealed that the synthesized nanoparticles were spherical, with a size range of 14–24 nm. Energy dispersive X-ray analysis and elemental mapping were used to observe Mn, O, C, H, and N. Fourier-transform infrared spectroscopy confirmed the presence of hydroxyl, carboxyl, and amino groups on the surface of the nanoparticles. The kinetics and isotherms were compared and it was found that the pseudo-second-order and Langmuir isotherm were the best fit, with R2 values of 0.99. The thermodynamic study demonstrated that the adsorption was endothermic and spontaneous. These findings indicate that chitosan functionalized nanoparticles have a better Pb(II) removal efficiency (94.40%), making them an eco-friendly and cost-effective alternative for wastewater treatment.HighlightsChitosan functionalized nanoadsorbent was synthesized through green route.Sorption mechanism explored through isotherm, kinetics, and thermodynamic models.Synthesized adsorbent showed high Pb(II) removal capacity.

Abstract Wildfire impacts the global carbon cycle, property, harvestable timber, and public health. Canada saw a record fire season in 2023 with 14.9 Mha burned—over seven times the 1986–2022 average of 2.1 Mha. Here we utilize a new process-based wildfire module that explicitly represents fire weather, fuel type and availability, ignition sources, fire suppression, and vegetation’s climate response to project the future of wildfire in Canada. Under rapid climate change (shared socioeconomic pathway [SSP] 370 & 585) simulated annual burned area in the 2090 s reaches 10.2 ± 2.1 to 11.7 ± 2.4 Mha, approaching the 2023 fire season total. However, climate change below a 2 °C global target (SSP126), keeps the 2090 s area burned near modern (2004–2014) norms. The simulated area burned and carbon emissions are most sensitive to climate drivers and lightning but future lightning activity is a key uncertainty.

Abstract Background High-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated if smoking and/or drinking augment the molecular mechanisms of cervical carcinogenesis and defined a potential therapeutic approach for their attenuation. Methods The impact of benzo[a]pyrene (B[a]P) and/or ethanol (EtOH) exposure on cervical cancer cells was assessed by measuring changes in their cell migration and invasion characteristics. Expression of HPV16 E6/E7, NF-κB, cytokines, and inflammation mediators was determined using qRT-PCR, immunoblotting, ELISA, luciferase reporter assay, and confocal microscopy. Herein, we used curcumin (Cur), and PLGA nanoparticle formulation of curcumin (PLGA-Cur) and determined effectiveness of free Cur and PLGA-Cur formulation on smoking and drinking activated NF-κB/IL-6 mediated inflammatory signaling pathways using in vitro cervical cancer models. Results Treatments with B[a]P and/or EtOH altered the expression of HPV16 E6/E7 oncogenes and EMT markers in cervical cancer cells; it also enhanced migration and invasion. In addition, B[a]P and/or EtOH exposure promoted inflammation pathways through TNF-α and NF-κB signaling, leading to IL-6 upregulation and activation of VEGF. The molecular effects caused by B[a]P and/or EtOH exposure were effectively attenuated by curcumin (Cur)/PLGA-Cur treatment. Conclusions These data suggest a molecular link between smoking, drinking, and HPV infectivity in cervical carcinogenesis. In addition, attenuation of these effects by treatment with Cur/PLGA-Cur treatment, implies the role of curcumin in cervical cancer prevention and treatment.

Abstract Background This study evaluated the performance of generative artificial intelligence (AI) models on the Orthopaedic In‐Training Examination (OITE), an annual exam administered to U.S. orthopaedic residency programs. Methods ChatGPT 3.5 and Bing AI GPT 4.0 were evaluated on standardised sets of multiple‐choice questions drawn from the American Academy of Orthopaedic Surgeons OITE online question bank spanning 5 years (2018–2022). A total of 1165 questions were posed to each AI system. The performance of both systems was standardised using the latest versions of ChatGPT 3.5 and Bing AI GPT 4.0. Historical data of resident scores taken from the annual OITE technical reports was used as a comparison. Results Across the five datasets, ChatGPT 3.5 scored an average of 55.0% on the OITE questions. Bing AI GPT 4.0 scored higher with an average of 80.0%. In comparison, the average performance of orthopaedic residents in national accredited programs was 62.1%. Bing AI GPT 4.0 outperformed ChatGPT 3.5 and Accreditation Council for Graduate Medical Education examinees, and analysis of variance analysis demonstrated p

Anxiety is a widespread and serious mental health issue that has been exacerbated by the COVID-19 pandemic and other stressors. In this study, we explore how online behavior data from Google and YouTube can be used to infer anxiety levels in individuals. We collected and processed digital traces from nearly 100 participants over eight weeks and applied various machine learning techniques to extract features and build predictive models. We found that combining data from multiple media modalities can yield highly accurate predictive models for anxiety as self-reported by a clinical GAD-7 scale (AUC > 0.86). We also found that the semantic categories of online engagement can affect the predictive performance of the models. This study contributes to the field of computational social science and digital mental health and demonstrates the potential of using online behavior data to monitor psychological well-being and design interventions for anxiety.

Key Clinical Message Be aware of potential severe interactions between aged honey containing grayanotoxins and alcohol. Such combinations can exacerbate symptoms like syncope and hypotension, especially in elderly patients with pre‐existing conditions, necessitating careful evaluation and management.

Background: The incidence of meningoencephalitis (ME) in India is poorly understood, and the exact etiological diagnosis is often not possible. This study was planned to elucidate the bacterial and viral etiological diagnosis of ME in children less than 5 years of age. Materials and Methods: The present study was conducted in Virus Research and Diagnostic Laboratory (VRDL), Department of Microbiology, King George’s Medical University, Lucknow, from July 2020 to June 2022. Serum, cerebrospinal fluid (CSF), and nose/throat swabs were collected from all the enrolled cases of meningoencephalitis in children below 5 years of age and tested for various etiological agents by ELISA and/or real-time PCR. Results: Of 130 enrolled cases, 50 (38.5%) cases tested positive for one or more etiological agents. Etiological agents of ME detected were Japanese encephalitis virus (JEV) (8.46%), adenovirus (6.92%), influenza virus (5.38%), dengue virus (3.85%), Parvo B-19 virus (3.08%), Orientia tsutsugamushi (3.08%), Herpes Simplex Virus-1 (HSV-1) (1.54%), measles virus (1.54%), and Varicella-Zoster Virus (VZV) (1.54%). Rubella virus, Chikungunya virus (CHKV), Mumps virus, Enteroviruses, Parecho virus, John Cunningham virus (JC), BK virus, Nipah virus, Kyasanur Forest Disease virus (KFD), Chandipura virus, Herpes Simplex Virus (HSV-2), SARS CoV-2, N. Meningitides, and H. Influenzae were tested but not detected in any of the cases. Conclusion: We identified the etiological agents in 50/130 (38.5%) suspected ME cases in children less than 5 years of age, using molecular and ELISA-based diagnostic methods. The four most common pathogens detected were JEV, adenovirus, influenza virus, and dengue virus.

α-synuclein (αSyn) is a presynaptic and nuclear protein that aggregates in important neurodegenerative diseases such as Parkinson's Disease (PD), Parkinson's Disease Dementia (PDD) and Lewy Body Dementia (LBD). Our past work suggests that nuclear αSyn may regulate forms of DNA double-strand break (DSB) repair in HAP1 cells after DNA damage induction with the chemotherapeutic agent bleomycin1. Here, we report that genetic deletion of αSyn specifically impairs the non-homologous end-joining (NHEJ) pathway of DSB repair using an extrachromosomal plasmid-based repair assay in HAP1 cells. Notably, induction of a single DSB at a precise genomic location using a CRISPR/Cas9 lentiviral approach also showed the importance of αSyn in regulating NHEJ in HAP1 cells and primary mouse cortical neuron cultures. This modulation of DSB repair is regulated by the activity of the DNA damage response signaling kinase DNA-PKcs, since the effect of αSyn loss-of-function is reversed by DNA-PKcs inhibition. Together, these findings suggest that αSyn plays an important physiologic role in regulating DSB repair in both a transformed cell line and in primary cortical neurons. Loss of this nuclear function may contribute to the neuronal genomic instability detected in PD, PDD and LBD and points to DNA-PKcs as a potential therapeutic target.

BackgroundIn the digital age, large language models (LLMs) like ChatGPT have emerged as important sources of health care information. Their interactive capabilities offer promise for enhancing health access, particularly for groups facing traditional barriers such as insurance and language constraints. Despite their growing public health use, with millions of medical queries processed weekly, the quality of LLM-provided information remains inconsistent. Previous studies have predominantly assessed ChatGPT’s English responses, overlooking the needs of non–English speakers in the United States. This study addresses this gap by evaluating the quality and linguistic parity of vaccination information from ChatGPT and the Centers for Disease Control and Prevention (CDC), emphasizing health equity. ObjectiveThis study aims to assess the quality and language equity of vaccination information provided by ChatGPT and the CDC in English and Spanish. It highlights the critical need for cross-language evaluation to ensure equitable health information access for all linguistic groups. MethodsWe conducted a comparative analysis of ChatGPT’s and CDC’s responses to frequently asked vaccination-related questions in both languages. The evaluation encompassed quantitative and qualitative assessments of accuracy, readability, and understandability. Accuracy was gauged by the perceived level of misinformation; readability, by the Flesch-Kincaid grade level and readability score; and understandability, by items from the National Institutes of Health’s Patient Education Materials Assessment Tool (PEMAT) instrument. ResultsThe study found that both ChatGPT and CDC provided mostly accurate and understandable (eg, scores over 95 out of 100) responses. However, Flesch-Kincaid grade levels often exceeded the American Medical Association’s recommended levels, particularly in English (eg, average grade level in English for ChatGPT=12.84, Spanish=7.93, recommended=6). CDC responses outperformed ChatGPT in readability across both languages. Notably, some Spanish responses appeared to be direct translations from English, leading to unnatural phrasing. The findings underscore the potential and challenges of using ChatGPT for health care access. ConclusionsChatGPT holds potential as a health information resource but requires improvements in readability and linguistic equity to be truly effective for diverse populations. Crucially, the default user experience with ChatGPT, typically encountered by those without advanced language and prompting skills, can significantly shape health perceptions. This is vital from a public health standpoint, as the majority of users will interact with LLMs in their most accessible form. Ensuring that default responses are accurate, understandable, and equitable is imperative for fostering informed health decisions across diverse communities.

Metarrestin (ML246) is a first-in-class pyrrole–pyrimidine-derived small molecule that selectively targets the perinucleolar compartment (PNC). PNC is a distinct subnuclear structure predominantly found in solid tumor cells. The occurrence of PNC demonstrates a positive correlation with malignancy, serving as an indicator of tumor aggressiveness, progression, and metastasis. Various promising preclinical results have led to the clinical translation of metarrestin into a first-in-human trial. This review aims to summarize (i) the current understanding of the structure and function of PNC and its role in cancer progression and metastasis, (ii) key findings from studies examining the effect of metarrestin on various cancers across the translational spectrum, including in vitro, in vivo, and human clinical trial studies, and (iii) the pharmaceutical relevance of metarrestin as a promising anticancer candidate. Furthermore, our molecular docking and MD simulation studies show that metarrestin binds to eEF1A1 and eEF1A2 with a strong and stable affinity and inhibits eEF1A2 more efficiently compared to eEF1A1. The promising results from preclinical studies suggest that metarrestin has the potential to revolutionize the treatment of cancer, heralding a paradigm shift in its therapeutic management.

The Programme for International Student Assessment (PISA) is a global survey conducted by the Organisation for Economic Co-operation and Development (OECD) to assess educational systems by evaluating the academic performance of 15-year-old school students in mathematics, science, and reading. In PISA 2022, 13,437 students from Australia participated in the test. While the PISA main questionnaire assesses the subject knowledge, the student background questionnaire solicits contextual information such as school climate, learner characteristics, and socioeconomic status. This study analyses how these contextual variables predict student achievement using the machine-learning models Ridge Linear Regression, K-Nearest Neighbours, Decision Trees, eXtreme Gradient Boosting, and Support Vector Machines, and it reports the evaluation matrices and the most accurate model in predicting student achievement. The analysis shows that contextual variables are associated with student achievement and account for 42% of the variance in achievement. In addition to evaluating multiple machine-learning regressors, Shapley Additive Explanation (SHAP) analysis is conducted to explain the model predictions and evaluate feature importance. Using SHAP analysis, this paper demonstrates how educators and school administrators may effectively interpret the machine-learning results and devise strategies for student success.

The present work focuses on the impact of expanded graphite (EG) nano-powder along with spark-on-duration (Ton) and spark-off-duration (Toff), and current as factors on increasing material removal rate (MRR), reduction of surface roughness (SR), tool wear rate (TWR), dimensional deviation (DD), and surface defects for Ni55.8Ti. Taguchi’s design having 4 factors at 3 levels was employed to perform the experimental trials. ANOVA has successfully validated the developed regression equations. EDM factors of PC, Toff, current, and Toff were found to be the largest contributing factors with the involvement of 76.91 %, 38.40 %, 34.36 %, and 44.54 % for MRR, TWR, SR, and DD respectively. TLBO algorithm was used in the present work to tackle the conflicting situation and to optimize the response variables. The simultaneous optimization conducted through the Teaching-learning-based optimization technique has yielded optimal parameters setting of Ton at 7 µs, Toff at 5 µs, PC at 1.5 g/L, and current at 10 A by giving optimal response values at MRR of 42.82 mm3/min, TWR of 0.4039 mm3/min, SR of 3.71 µm, and DD of 92.65 µm. Lastly, Scanning electron microscopy was utilized to check EG nano-powder significance on the machined parts' surface morphology.

The optimum utilisation of explosive energy in the rock blasting operation is a prime challenge for the blast designers. The explosive energy in this operation is used for movement of burden. The optimum fracturing of the rock mass to meet the production demand takes place along tension. In the process of blasting, the detonation pressure of the explosives in the blasthole induces shock wave to the rock mass. The propagating shock wave is initially compressive in nature and becomes tensile after being reflected from the free face. The extent of tensile damage zone would give the optimum burden for blasting. The explosive properties along with the rock mass properties and charge configuration influences the extent of tensile damage zone. In this study, an empirical relation has been developed for estimation of blast induced tensile damage zone. The experimental trials were conducted at a coal mine using two different types of explosives for the validation of the developed empirical relation. The ground vibration predictors were developed using the data of experimental trials. The induced damage zone was computed using empirical relation proposed by Forsyth (1993) and developed ground vibration predictors. The estimated damage zone using developed empirical predictor and Forsyth relation were compared. The difference in the induced damage zone using two approaches is within 10%. The predicted values using developed empirical relation are accurate with RMSE value of 0.227 m. Hence, the developed empirical relation would be beneficial for estimation of blast induced crack zone.

Abstract The ability to form reconstructions beyond line-of-sight view could be transformative in a variety of fields, including search and rescue, autonomous vehicle navigation, and reconnaissance. Most existing active non-line-of-sight (NLOS) imaging methods use data collection steps in which a pulsed laser is directed at several points on a relay surface, one at a time. The prevailing approaches include raster scanning of a rectangular grid on a vertical wall opposite the volume of interest to generate a collection of confocal measurements. These and a recent method that uses a horizontal relay surface are inherently limited by the need for laser scanning. Methods that avoid laser scanning to operate in a snapshot mode are limited to treating the hidden scene of interest as one or two point targets. In this work, based on more complete optical response modeling yet still without multiple illumination positions, we demonstrate accurate reconstructions of foreground objects while also introducing the capability of mapping the stationary scenery behind moving objects. The ability to count, localize, and characterize the sizes of hidden objects, combined with mapping of the stationary hidden scene, could greatly improve indoor situational awareness in a variety of applications.

Emergency department (ED) visits for suicidal ideation or behavior have been increasing in all age groups, particularly younger adults. A rapid-acting treatment to reduce suicidal thinking, adapted for ED use, is needed. Previous studies have shown a single dose of ketamine can improve depression and suicidal ideation within hours. However, most studies used 40 min intravenous infusions which can be impractical in a psychiatric ED. The ER-Ketamine study we describe here is a randomized midazolam-controlled clinical trial (RCT; NCT04640636) testing intramuscular (IM) ketamine's feasibility, safety, and effectiveness to rapidly reduce suicidal ideation and depression in a psychiatric ED. A pre-injection phase involves screening, informed consent, eligibility confirmation, and baseline assessment of suicidal ideation, depression, and comorbidities. The randomized double-blind IM injection is administered in the ED under research staff supervision, vital sign monitoring, pharmacokinetic blood sampling, and clinical assessments. The post-injection phase occurs on a psychiatric inpatient unit with follow-up research assessments through four weeks post-discharge. Outcome measures are feasibility, safety, and effects on suicidal ideation and depression at 24 h post-injection, and through follow-up. The target sample is N = 90 adults in a major depressive episode, assessed by ED clinicians as warranting hospitalization for suicide risk. Here we report design, rationale, and preliminary feasibility and safety for this ongoing study. Demographics of the 53 participants (ages 18 to 65 years) randomized to date suggest a diverse sample tending towards younger adults.

Abstract Earth System Models (ESMs) project that the terrestrial carbon sink will continue to grow as atmospheric CO2 increases, but this projection is uncertain due to biases in the simulated climate and how ESMs represent ecosystem processes. In particular, the strength of the CO2‐fertilization effect, which is modulated by nutrient cycles, varies substantially across models. This study evaluates land carbon balance uncertainties for the Canadian Earth System Model (CanESM) by conducting simulations where the latest version of CanESM's land surface component is driven offline with raw and bias‐adjusted CanESM5 climate forcing data. To quantify the impact of nutrient limitation, we complete simulations where the nitrogen cycle is enabled or disabled. Results show that bias adjustment improves model performance across most ecosystem variables, primarily due to reduced biases in precipitation. Turning the nitrogen cycle on increases the global land carbon sink during the historical period (1995–2014) due to enhanced nitrogen deposition, placing it within the Global Carbon Budget uncertainty range. During the future period (2080–2099), the simulated land carbon sink increases in response to bias adjustment and decreases in response to the dynamic carbon‐nitrogen interaction, leading to a net decrease when both factors are acting together. The dominating impact of the nitrogen cycle demonstrates the importance of representing nutrient limitation in ESMs. Such efforts may produce more robust carbon balance projections in support of global climate change mitigation policies such as the 2015 Paris Agreement.

Background Data. Spinal infections are major clinical problems with a substantial financial burden on healthcare systems. Recent increases in primary pyogenic spine infections can be attributed to the opioid epidemic and an aging and increasingly unhealthy population. Immunocompromise, diabetes, and malignancy all predispose patients to spine infections. Purpose. To identify the differences in patient factors, presentation, treatment course, and outcomes of intravenous drug users (IVDA) vs. nonusers (non-IVDA) presenting with pyogenic spinal infections. Study Design/Setting. Retrospective case series. Methods. We identified all cases involving spinal infections at our institution between May 2017 and January 2023. Postsurgical infections were excluded, and patients were separated into IVDA and non-IVDA groups. The patient charts were reviewed and analyzed for statistical or clinically significant differences using RStudio (2019 version 3.6.2). Our institutional review board approved this study, IRB# 2020-277, iRISID-2023-1384. Results. Fifty patients (29 males and 21 females) with primary pyogenic spinal infections were included in our study. There were fourteen patients (28.0%) in the IVDA group. The mean age in the IVDA group was 50.6 vs. 61.9 years (p

In the present study, the Gas metal arc welding (GMAW) based Wire-arc additive manufacturing (WAAM) process was preferred for the fabrication of multi-layered structures and their investigations of mechanical properties on metal core wire. Based on literature work, preliminary trials, machine limits, travel speed (TS), voltage (V), and gas mixture ratio (GMR) were identified as machining parameters along with output factors of bead width (BW), bead height (BH), and depth-of-penetration (DOP). Experiments were conducted by following the Box-Behnken design. The feasibility of the generated non-linear regression models has been validated through the statistical analysis of variance and residual plots. The multi-layered structure has been successfully fabricated at the optimized parametric settings of TS at 24 mm/s; the voltage at 24 V, and GMR at 1 which was obtained through the heat transfer search (HTS) algorithm. The fabricated structure was observed to be uniform. The structure exhibited uniform bead-on-bead deposition for the deposited layers. The fabricated multi-layered structure underwent a detailed microstructural and mechanical examinations. Microstructural examination revealed dense needles at the bottom section of the structure as compared to the top section, as the bottom section undergoes multiple heating and cooling cycles. When comparing the multilayer structure to the metal core wire, all the properties exhibited favorable tensile characteristics. The obtained strength from the impact test results highlights the impressive ductility of the multi-layer deposition. Fractography of tensile and impact test specimens has shown the occurrences of larger dimples and suggested a ductile fracture. Lastly, the hardness value in all the sections of the built structure was observed to be uniform, suggesting uniform deposition across the built multi-layer structure. The authors consider the current work will be highly beneficial for users in fabricating multi-layer structures at optimized parametric settings and their investigations for mechanical properties for metal core wire.

Cabozantinib is a tyrosine kinase inhibitor that has been approved as therapy for several solid tumors, including metastatic renal cell carcinoma, hepatocellular carcinoma, and differentiated thyroid cancer. To prepare this review, we comprehensively searched various websites, including the United States Food and Drug Administration, the European Medicine Agency Drug Manual, PubMed, Science Direct, and UpToDate using the search terms, “cabozantinib,” “renal cell carcinoma,” “hepatocellular carcinoma,” “differentiated thyroid cancer,” and “medullary thyroid cancer.” We shortlisted all the full-text articles published between 2011 and 2022. Out of a total of 788 manuscripts identified, we included 52. This review of cabozantinib details the pharmacodynamics, pharmacokinetics, clinical indications, adverse effects, safety, and the key research trials that investigated the use of cabozantinib. We have discussed the available clinical trial data and real-world outcomes, both with respect to the efficacy and safety of cabozantinib.

Penalty functions or regularization terms that promote structured solutions to optimization problems are of great interest in many fields. We introduce MEGS, a nonconvex structured sparsity penalty that promotes mutual exclusivity between components in solutions to optimization problems. This enforces, or promotes, 1-sparsity within arbitrary overlapping groups in a vector. The mutual exclusivity structure is represented by a matrix ${\bf {S}}$. We discuss the design of ${\bf {S}}$ from engineering principles and show example use cases including the modeling of occlusions in 3D imaging and a total variation variant with uses in image restoration. We also demonstrate synergy between MEGS and other regularizers and propose an algorithm to efficiently solve problems regularized or constrained by MEGS.

The probiotic-derived siderophore, ferrichrome, enhances anti-tumor immunity and improves the efficacy of checkpoint immunotherapy in a model of pancreatic cancer by repolarizing tumor-associated macrophages to a immunostimulatory M1 phenotype.

Summary: A lack of diversity in genomics for health continues to hinder equitable leadership and access to precision medicine approaches for underrepresented populations. To avoid perpetuating biases within the genomics workforce and genomic data collection practices, equity, diversity, and inclusion (EDI) must be addressed. This paper documents the journey taken by the Global Alliance for Genomics and Health (a genomics-based standard-setting and policy-framing organization) to create a more equitable, diverse, and inclusive environment for its standards and members. Initial steps include the creation of two groups: the Equity, Diversity, and Inclusion Advisory Group and the Regulatory and Ethics Diversity Group. Following a framework that we call “Reflected in our Teams, Reflected in our Standards,” both groups address EDI at different stages in their policy development process.

Summary: To explore mechanisms of response to combined PD-1/CTLA-4 immune checkpoint blockade (ICB) treatment in individual cell types, we generated scRNA-seq using a mouse model of invasive urothelial carcinoma with three conditions: untreated tumor, treated tumor, and tumor treated after CD4+ T cell depletion. After classifying tumor cells based on detection of somatic variants and assigning non-tumor cell types using SingleR, we performed differential expression analysis, overrepresentation analysis, and gene set enrichment analysis (GSEA) within each cell type. GSEA revealed that endothelial cells were enriched for upregulated IFN-g response genes when comparing treated cells to both untreated cells and cells treated after CD4+ T cell depletion. Functional analysis showed that knocking out IFNgR1 in endothelial cells inhibited treatment response. Together, these results indicated that IFN-g signaling in endothelial cells is a key mediator of ICB induced anti-tumor activity.

Abstract Single cell RNA sequencing studies identified novel neurodegeneration-associated microglial (MGnD/DAM) subtypes activated around cerebral amyloid plaques. Micro-RNA (miR)-155 of the TREM2-APOE pathway was shown to be a key transcriptional regulator of MGnD microglial phenotype. Despite growing interest in studying manifestations of Alzheimer’s disease (AD) in the retina, a CNS organ accessible to noninvasive high-resolution imaging, to date MGnD microglia have not been studied in the AD retina. Here, we discovered the presence and increased populations of Clec7a+ and Galectin-3+ MGnD microglia in retinas of transgenic APPSWE/PS1L166P AD-model mice. Conditionally targeting MGnD microglia by miR-155 ablation via the tamoxifen-inducible CreERT2 system in APPSWE/PS1L166P mice diminished retinal Clec7a+ and Galectin-3+ microglial populations while increasing homeostatic P2ry12+ microglia. Retinal MGnD microglia were often adhering to microvessels; their depletion protected the inner blood-retina barrier and reduced vascular amyloidosis. Microglial miR-155 depletion further limits retinal inflammation. Mass spectrometry analysis revealed enhanced retinal PI3K-Akt signaling and predicted IL-8 and Spp1 decreases in mice with microglia-specific miR-155 knockout. Overall, this study identified MGnD microglia in APPSWE/PS1L166P mouse retina. Transcriptional regulation of these dysfunctional microglia mitigated retinal inflammation and vasculopathy. The protective effects of microglial miR-155 ablation should shed light on potential treatments for retinal inflammation and vascular damage during AD and other ocular diseases.

The global net land sink is relatively well constrained. However, the responsible drivers and above/below-ground partitioning are highly uncertain. Model issues regarding turnover of individual plant and soil components are responsible.

Nanotechnology has become one of the most rapid, innovative, and adaptable sciences in modern science and cancer therapy. Traditional chemotherapy has limits owing to its non-specific nature and adverse side effects on healthy cells, and it remains a serious worldwide health issue. Because of their capacity to specifically target cancer cells and deliver therapeutic chemicals directly to them, nanoparticles have emerged as a viable strategy for cancer therapies. Nanomaterials disclose novel properties based on size, distribution, and shape. Biosynthesized or biogenic nanoparticles are a novel technique with anti-cancer capabilities, such as triggering apoptosis in cancer cells and slowing tumour growth. They may be configured to deliver medications or other therapies to specific cancer cells or tumour markers. Despite their potential, biosynthesized nanoparticles confront development obstacles such as a lack of standardisation in their synthesis and characterization, the possibility of toxicity, and their efficiency against various forms of cancer. The effectiveness and safety of biosynthesized nanoparticles must be further investigated, as well as the types of cancer they are most successful against. This review discusses the promise of biosynthesized nanoparticles as a novel approach for cancer therapeutics, as well as their mode of action and present barriers to their development.

This study aimed to assess the phytochemical composition, in vitro antioxidant, cytotoxicity, and in vivo anti-inflammatory activities of the methanolic extract of Ailanthus excelsa (Simaroubaceae) stem bark and its fractions. Quantitative phytochemical analysis revealed that methanolic extract and all fractions contained a high level of flavonoids (20.40–22.91 mg/g QE), phenolics (1.72–7.41 mg/g GAE), saponins (33.28–51.87 mg/g DE), and alkaloids (0.21–0.33 mg/g AE). The antioxidant potential was evaluated in vitro using a range of assays, i.e., DPPH•, ABTS radical scavenging ability, and total antioxidant capacity. The chloroform and ethyl acetate fractions showed stronger antioxidant activity than the methanol extract. In vitro cytotoxic activity was investigated in three human tumor cell lines (A-549, MCF7 and HepG2) using the SRB assay. In addition, the in vivo anti-inflammatory effect was assessed by carrageenan-induced paw edema in rats. The chloroform fraction showed a more pronounced effect by effectively controlling the growth with the lowest GI50 and TGI concentrations. The human lung cancer cell line (A-549) was found to be more sensitive to the chloroform fraction. Furthermore, the chloroform fraction exhibited significant anti-inflammatory activity at a dose of 200 mg/kg in the latter phase of inflammation. Besides, methanol extract and ethyl acetate fraction revealed a significant cytotoxic and anti-inflammatory effects. The chloroform fraction of stem bark showed a strong anti-inflammatory effect in experimental animals and significant COX-2 inhibitory potential in the in vitro experiments. GC-MS analysis of chloroform fraction identified the phytochemicals like caftaric acid, 3,4-dihydroxy phenylacetic acid, arachidonic acid, cinnamic acid, 3-hydroxyphenylvaleric acid, caffeic acid, hexadeconoic acid, and oleanolic acid. The in-silico results suggest that identified compounds have better affinity towards the selected targets, viz. the BAX protein (PDB ID: 1F16), p53-binding protein Mdm-2 (PDB ID: 1YCR), and topoisomerase II (PDB ID: 1QZR). Amongst all, caftaric acid exhibited the best binding affinity for all three targets. Thus, it can be concluded that caftaric acid in combination with other phenolic compounds, might be responsible for the studied activity. Additional in vivo and in vitro studies are required to establish their exact molecular mechanisms and consider them as lead molecules in developing of valuable drugs for treating oxidative stress-induced disorders, cancers, and inflammations.

Abstract Tight regulation of immediate early gene (IEG) expression is important for synaptic plasticity, learning, and memory. Recent work has suggested that DNA double strand breaks (DSBs) may have an adaptive role in post-mitotic cells to induce IEG expression. Physiological activity in cultured neurons as well as behavioral training leads to increased DSBs and subsequent IEG expression. Additionally, infusion of etoposide—a common cancer treatment that induces DSBs—impairs trace fear memory. Here, we assessed the effects of hippocampal infusion of 60 ng of etoposide on IEG expression, learning, and memory in 3–4 month-old C57Bl/6J mice. Etoposide altered expression of the immediate early genes cFos and Arc in the hippocampus and impaired hippocampus-dependent contextual fear memory. These data add to the growing evidence that DSBs play an important role in IEG expression, learning, and memory, opening avenues for developing novel treatment strategies for memory-related disorders.

Excellent characteristics of Nitinol shape memory alloys (SMAs) makes them favourable for use in industrial applications. Precision machining of such advanced alloys becomes a key requirement for industrial applications. Conventional machining processes imposes many difficulties for nitinol SMAs. Electrical discharge machining (EDM) process is appropriate for fabricating intricate and complex profile geometries and also provides a better alternative for difficult-to-cut materials. Addition of nano-particles in an appropriate amount in the dielectric fluid improves the machining by producing good dimensional accuracy, higher productivity, and good surface finish for machining of newly developed advanced alloys. The current study investigated the performance of powder-mixed EDM of nitinol SMA with the considerations of design variables of current, pulse-on-time (Ton), nano-graphene powder concentration (PC), and pulse-off-time (Toff) on surface roughness, dimensional deviation (DD), and material removal rate (MRR). Taguchi's L9 (3ˆ4) design was employed to perform the experiments and Minitab 17 software was used for statistical analysis of design variables using ANOVA, residual plots, and main effect plots. ANOVA results depicted that PC, Ton, and Toff were identified to be the highest contributing parameters with 75.18%, 29.37%, and 45.72% to affect MRR, SR, and DD, respectively. Obtained results has depicted a preferred combined positive trend of increase in MRR with a simultaneous drop in SR and DD after the addition of nano-graphene PC. HST algorithm was used to optimize single and multiple responses. Validation trials were also conducted to reveal the ability and suitability of the HTS technique. Field emission scanning electron microscopy revealed the minor occurrence of resolidified debris particles, globules, micro-pores, and micro-cracks after the addition of nano-graphene PC at 2 g/L.

Age-related macular degeneration (AMD) is a leading cause of vision loss, and there is no approved treatment for AMD with geographic atrophy. Here, the authors used transcriptomic and proteomic analyses of patient induced pluripotent stem cell-derived retinal pigment epithelium to better understand disease mechanisms.

We present the spectral and timing study of the bright neutron star low-mass X-ray binary GX 5-1 using AstroSat/Large Area X-ray Proportional Counter (LAXPC) and Soft X-ray Telescope observations conducted in 2018. During the observation, the source traces out the complete horizontal branch (HB) and normal branch (NB) of the Z-track in the hardness–intensity diagram (HID). Understanding the spectral and temporal evolution of the source along the Z-track can probe the accretion process in the vicinity of a neutron star. Spectral analysis was performed in the 0.7–20 keV energy range for different segments in the HID using a multitemperature disk blackbody with an average temperature, kT _in ∼ 0.47, and a thermal Comptonization model. It is found that the optical depth of the corona drops from ∼7.07 in HB to ∼2.61 in NB. The timing analysis using the LAXPC instrument indicates the presence of quasiperiodic oscillations in HB and NB of the Z-track. The observed QPO frequencies are similar to the characteristic frequencies of horizontal branch oscillations (HBOs) and normal branch oscillations (NBOs). The HBO frequency increases from ∼12 to 40 Hz toward the hard apex. NBOs are observed at ∼5 Hz. The timing studies conducted in soft and hard bands indicate the association of HBO and NBO origin with the nonthermal component. Further research could explore the implications of this relationship for understanding the dynamics of accretion onto neutron stars.

The rising adoption of electric vehicles (EVs) has exacerbated the need for efficient, user-friendly charging options. Wireless rapid charging presents a viable alternative to standard plug-in systems, with the possibility for greater convenience and reduced wear on connectors. This article covers the current state and future prospects of wireless fast charging systems for EVs, concentrating on the underlying principles, recent breakthroughs, and forthcoming innovations. Key challenges, such as efficiency, cost, safety, and infrastructure integration, are thoroughly analysed. The paper also reviews existing implementations and case cases, highlighting their performance and scalability. Additionally, it examines regulatory and standardization challenges that effect the development and deployment of wireless charging systems. Future research directions are offered to address current constraints and further enhance the technology. Overall, this report gives a detailed analysis of the potential of wireless fast charging to change EV infrastructure and explains the actions necessary to overcome present impediments and reach its full potential.

Soil contains several organic, and inorganic substances and a large number of bacterial diversity. This bacterial diversity is also involved in biomass degradation and plant growth promotion. Metagenomic sequencing was used to analyze bacterial diversity in the rice field soil and sludge samples. Amplicon sequencing of the V3-V4 region of the 16S rRNA gene revealed that representative sequences clustered were 0.4 million in both rice and sludge samples. The Venn diagram demonstrates the overall identified OTUs was 359 Operational Taxonomic Units (OTUs). OTUs were classified into more than 30 phyla, 50 classes, and 90 genera. The metagenomic analysis revealed that 82 and 85 taxa are exclusively unique to the bacterial communities of the rice and sludge soils, respectively. The metagenomic study also revealed that Proteobacteria, Bacteroidetes, Chloroflexi, Acidobacteria and other unknown bacteria were reported in 16S rRNA Illumina MiSeq in the sludge and rice soil samples. The most abundant groups in rice field soil were Proteobacteria, Chloroflexi, Acidobacteria, Actinobacteria, and Bacteroidetes which increase the soil nutrient and influence the growth of the plants. Bacteroidetes are the most dominant group in sludge soil than rice field soil. This comparative analysis provides insights into the ecological roles and adaptive strategies of soil bacteria in different environmental contexts, offering valuable information for sustainable soil management and bioremediation practices.

We present near-simultaneous X-ray and optical polarization measurements in the high synchrotron peaked (HSP) blazar Mrk 421. The X-ray polarimetric observations were carried out using Imaging X-ray Polarimetry Explorer (IXPE) on 2023 December 6. During IXPE observations, we also carried out optical polarimetric observations using 104 cm Sampurnanand telescope at Nainital and multiband optical imaging observations using 2 m Himalayan Chandra Telescope at Hanle. From model-independent analysis of IXPE data, we detected X-ray polarization with degree of polarization (Π _X ) of 8.5% ± 0.5% and an electric vector position angle (Ψ _X ) of 10.°6 ± 1.°7 in the 2−8 keV band. From optical polarimetry on 2023 December 6, in B , V , and R bands, we found values of Π _B = 4.27% ± 0.32%, Π _V = 3.57% ± 0.31%, and Π _R = 3.13% ± 0.25%. The value of Π _B is greater than that observed at longer optical wavelengths, with the degree of polarization suggesting an energy-dependent trend, gradually decreasing from higher to lower energies. This is consistent with that seen in other HSP blazars and favors a stratified emission region encompassing a shock front. The emission happening in the vicinity of the shock front will be more polarized due to the ordered magnetic field resulting from shock compression. The X-ray emission, involving high-energy electrons, originates closer to the shock front than the optical emission. The difference in the spatial extension could plausibly account for the observed variation in polarization between X-ray and optical wavelengths. This hypothesis is further supported by the broadband spectral energy distribution modeling of the X-ray and optical data.

In the present study, a comprehensive parametric analysis was carried out using the electrical discharge machining of Ti6Al4V, using pulse-on time, current, and pulse-off time as input factors with output measures of surface roughness and material removal rate. The present study also used two different nanopowders, namely alumina and nano-graphene, to analyze their effect on output measures and surface defects. All the experimental runs were performed using Taguchi’s array at three levels. Analysis of variance was employed to study the statistical significance. Empirical relations were generated through Minitab. The regression model term was observed to be significant for both the output responses, which suggested that the generated regressions were adequate. Among the input factors, pulse-off time and current were found to have a vital role in the change in material removal rate, while pulse-on time was observed as a vital input parameter. For surface quality, pulse-on time and pulse-off time were recognized to be influential parameters, while current was observed to be an insignificant factor. Teaching–learning-based optimization was used for the optimization of output responses. The influence of alumina and nano-graphene powder was investigated at optimal process parameters. The machining performance was significantly improved by using both powder-mixed electrical discharge machining as compared to the conventional method. Due to the higher conductivity of nano-graphene powder, it showed a larger improvement as compared to alumina powder. Lastly, scanning electron microscopy was operated to investigate the impact of alumina and graphene powder on surface morphology. The machined surface obtained for the conventional process depicted more surface defects than the powder-mixed process, which is key in aeronautical applications.

Abstract Background Based on an increased prevalence of diabetes, asthma and hypertension among women in reproductive age, understanding the risk factors of non-communicable diseases (NCDs) is crucial to inform policy and program interventions to address the problem. In this study, we empirically assessed the associations of behavioural factors such as alcohol consumption and tobacco use and a variety of socioeconomic characteristics with prevalence of NCDs in adult women. Methods The data were derived from the National Family Health Survey conducted in 2015–16. The effective sample size for the present paper was 699,686 women aged 15–49 years in India. Descriptive statistics along with bivariate analysis were conducted to find the preliminary results. Additionally, multivariable logistic regression analysis was conducted to find the relationship between NCDs and behavioural factors such as alcohol consumption and tobacco use. Moreover, population attributable risk was estimated in the present study. Results It was revealed that 15.9% of women had any of the NCDs. A proportion of 0.8% of women smoked tobacco whereas 5.5% of women consumed smokeless tobacco. Also, a proportion of 1.2% of women consumed alcohol in the current study. The odds of having NCDs among women who smoked tobacco, consumed smokeless tobacco and consume alcohol were 16, 8 and 20% significantly higher than the odds of having NCDs among women who did not smoke tobacco, consume smokeless tobacco and consume alcohol respectively. The population attributable risk of having NCDs was 1.8% (p

Capillary electrophoresis (CE) is widely used for the impurity profiling of drugs that contain stereochemical centers in their structures, analysis of biomolecules, and characterization of biopharmaceuticals. Currently, CE is the method of choice for the analysis of foodstuffs and the determination of adulterants. This article discusses the general theory and instrumentation of CE as well as the classification of various CE techniques. It also presents an overview of research on the applications of different CE techniques in the impurity profiling of drugs in the past decade. The review briefly presents a comparison between CE and liquid chromatography methods and highlights the strengths of CE using drug compounds as examples. This review will help scientists, fellow researchers, and students to understand the applications of CE techniques in the impurity profiling of drugs.

Abstract Meiosis is a specialized cell division that halves the number of chromosomes in two consecutive rounds of chromosome segregation. In angiosperm plants is meiosis followed by mitotic divisions to form rudimentary haploid gametophytes. In Arabidopsis, termination of meiosis and transition to gametophytic development are governed by TDM1 and SMG7 that mediate inhibition of translation. Mutants deficient in this mechanism do not form tetrads but instead undergo multiple cycles of aberrant nuclear divisions that are likely caused by the failure to downregulate cyclin dependent kinases during meiotic exit. A suppressor screen to identify genes that contribute to meiotic exit uncovered a mutation in cyclin‐dependent kinase D;3 (CDKD;3) that alleviates meiotic defects in smg7 deficient plants. The CDKD;3 deficiency prevents aberrant meiotic divisions observed in smg7 mutants or delays their onset after initiation of cytokinesis, which permits formation of functional microspores. Although CDKD;3 acts as an activator of cyclin‐dependent kinase A;1 (CDKA;1), the main cyclin dependent kinase that regulates meiosis, cdkd;3 mutation appears to promote meiotic exit independently of CDKA;1. Furthermore, analysis of CDKD;3 interactome revealed enrichment for proteins implicated in cytokinesis, suggesting a more complex function of CDKD;3 in cell cycle regulation.

Abstract The persimmon fruit (Diospyros kaki) belonging to the family Ebenaceae, is a famous conventional Korean medicinal herb. Calyx of persimmon has been used to prepare herbal drinks in Korea, China, and Japan due to its various functional ingredients, including fructose, glucose, and triterpenoid. In addition, persimmon is generally used as traditional medicine in Korea for the treatment of asthma, chronic bronchitis, and cough. Various useful constituents have been isolated and characterized from Diospyros species, including naphthaquinones, triterpenoids, and steroids. The fruit's nutritional composition comprising 80.3% water, 0.58% protein, 0.19% total lipids, 18.6% total carbohydrates and some minerals, and up to 1.48 g and 7.5 mg total dietary fiber, and ascorbic acid, respectively. Specifically, a flavonoid, fisetin, present in persimmon is associated with killing breast cancer cells without harming normal breast cells, thus contributing to the programmed eradication of colon and prostate cancer cells. Some other notable compounds reported from the various parts of the plant and their extracts have significant pharmaceutical values due to their antioxidant, anticancer, anti‐aging, and cytotoxic activities. It is, therefore, high time to promote the consumption of exotic fruits with a rich source of natural antioxidants as a functional supplement to the human diet, with a view to increase the disease protection efficacy.

In this work, the refrigerant R1233zd(E) (A1 ASHRAE safety code) is investigated for the possible substitution of refrigerant R161 (A2 ASHRAE safety code) in a cascade refrigeration system. The high-temperature circuit refrigerant R1233zd(E) is evaluated with the low-temperature circuit refrigerants R41 and R170 for thermo-economic consideration. A comparative analysis of the refrigerant combination R41-R1233zd(E) and R170-R1233zd(E) presents exergy efficiency and total plant cost as evaluation criteria. Pareto solutions are obtained for the thermo-economic objectives for each pair of refrigerants. A decision-making method is adopted to identify the best result from the Pareto solutions obtained. The effects of operating variables such as evaporator temperature, condenser temperature, LTC condensing temperature, and temperature difference of cascade condenser are evaluated. The sensitivity of the operating variables on thermo-economic objectives is also evaluated. The comparative results reveal that for the same total cost rate of the system (68,615 $/year), the exergy efficiencies of the CRS are 63.08% (R170-R161), 64.04% (R41-R161), 64.93% (R170-R1233zd(E)), and 65.81% (R41-R1233zd(E)). Also, the R1233zd(E) based CRS operates with a lower total cost rate than the R161-based system.

Objective: To evaluate patient demographic characteristics and risk factors for mortality during the first and the second wave among COVID-19 patients in a tertiary care hospital of India. Methods: Data were taken from the hospital’s electronic system for COVID-19 patients from August 2020 to December 2020, and the second from January 2021 to May 2021. The mortality rate, demographic and clinical characteristics, laboratory profile, and reasons for the death of the two waves were retrieved and compared, and the risk factors of the two waves were determined. Results: In the first wave, 1 177 COVID-19 cases visited the hospital and 96 (8.2%) died. In comparison, the death rate in the second wave was significantly higher (244/2 038, 12.0%) (P

In this paper, the physical layer security (PLS) challenges for a decode and forward (DF) based dual hop mixed free space optical (FSO) / radio frequency (RF) communication system in the presence of multiple eavesdroppers has been investigated. In order to improve the PLS of the energy efficient co-operative communication system, diversity combining techniques have been introduced at the destination node. In addition to this, collusion and non collusion eavesdropper scenarios are considered to make the system more practical. The FSO and RF links are assumed to experience independent Málaga ($\mathcal {M}$) and Nakagami-$m$ fading distributions, respectively. Additionally, the FSO link model considers the impact of boresigt and non-zero boresight pointing errors and type of optical demodulation scheme. To investigate the security performance, the lower bound for the secrecy outage probability (SOP) and effective secrecy throughput (EST) have been obtained in terms of Meijer’s G function. Thereafter, asymptotic expressions have been derived for the considered system and the numerical results have been verified by the Monte-Carlo simulation method. Finally, we have analyzed the secrecy energy efficiency (SEE) based on secrecy rate ($R_s$) of the considered system to provide practical insights into the effect of major parameters on the energy efficient secure transmission design.

Introduction: Veno-arterial extracorporeal membrane oxygenation (ECMO) is well-recognized treatment modality for patients with refractory cardiogenic shock. Uncomplicated cannulation is a prerequisite and basis for achieving a successful outcome in ECMO. Vascular access is obtained either by surgical cut-down. Common vascular access complications are bleeding and limb ischemia. Objective: To evaluate cannulation technique, the incidence of vascular complications, and their impact on the outcome. Methods: A retrospective data analysis conducted on 95 patients receiving ECMO from 2013 to 2020 was done. The patients were divided into two groups: no vascular access complications (non-VAC group) and vascular access complications (VAC group). The groups were compared related to the hospital and ICU stays and blood transfusion. Results: The patients in both groups were demographically and clinically comparable. The Non-VAC group had 75 patients, whereas the VAC group had a total of 20 patients. The main complication observed in the VAC group was bleeding from the cannulation site which required more blood transfusion than the non-VAC group (6.8 ± 1.02 vs 4.2 ± 1.26). Limb ischemia was another complication seen in the VAC group (4.2%, n = 4). Two patients had delayed bleeding after decannulation. The overall average length of stay in the hospital was statistically similar in both the groups (22 days in the VAC group vs 18 days in the non-VAC group), but the average ICU stay was more in the VAC group compared to the non-VAC group (18 days vs 12.06 days). Conclusion: Bleeding and limb ischemia are the important vascular access site complications, which increase blood transfusion requirements, ICU stay, and overall hospital stay.

The reasons for high morbidity and mortality with Corona virus disease (COVID-19) disease remain unanswered with extremes of manifestation and uncertainty of modes of transmission for which biomarkers are urgently needed for early prediction of severity and prompt treatment. We have reviewed publications from PubMed (years 2019–2021) analysing the biochemical, immune-inflammatory, nucleic acid, and cellular biomarkers that predict infection, disease progression in COVID-19 with emphasis on organ-specific damage. Our analysis of 65 biomarkers assessing the impact of SCoV-2 infection on five organs (lung, liver, cardiac, kidney, and neural) reported that increased levels of CRP, TNF-α, ferritin, IL-6, D-dimer, Procalcitonin, Fibrinogen to Albumin Ratio (FAR), and decrease platelet count (PC), lymphocyte count, leukocyte count, and CD4+/CD8+ ratio shows promising association in the early diagnosis, prediction of prognosis and severity disease and also correlates with cytokine storm a cardinal feature of COVID-19 progression. In the above scenario, this review has put forth the most promising biomarkers for COVID diagnosis and prognosis based on the reported literature. In recent year's chemically synthesized antibody-like biomolecules, aptamers were also used in the diagnosis of COVID-19 which could be preferably used for diagnosis over antibodies. Biomarkers including increase in free DNA and Fibrinogen-to-Albumin Ratio, CRP, PCT, and Ferritin along with a consequential decrease of CD3+ T, CD4+ T, CD8+ T, NK cells with corresponding increase in CD4+/CD8+ ratio following SARS CoV-2 infection has been consistently correlated with disease severity. Despite the two waves of COVID-19 pandemic, currently there is no standard clinical practice guideline for evaluating the severity of the devastating pandemic of COVID-19, hence these biomarkers will have immense relevance for the third and subsequent wave of COVID-19 and related pandemic.

In this paper, the physical layer security (PLS) analysis for a decode-and-forward (DF) protocol based multi-hop hybrid radio frequency (RF)/ free space optics (FSO) is presented. Herein, two different scenarios are considered for detecting the secured information at the destination. In the first scenario, at each hop, the received signals with higher secrecy capacity are selected. However, in the second scenario, the RF and FSO signals are simply decoded and forwarded to the next hop and selection is done at the last hop only. Each node in the system is connected to its subsequent node through parallel RF and FSO links. The FSO links and RF links are characterized by Málaga ($\mathcal {M}$) and Nakagami-$m$ composite distributions respectively. For both scenarios, the secrecy outage probability (SOP), strictly positive secrecy capacity (SPSC), intercept probability (IP), and effective secrecy throughput (EST) are obtained as performance metrics. These performance metrics are obtained by considering pointing error, different optical signal detection methods, turbulence effect, and the RF link fading parameter ($m$). Using the results, the security and reliability trade-off analysis is discussed for two scenarios. In addition, the asymptotic results are also obtained to study the system in depth. Further, the secrecy diversity order (SDO) and secrecy coding gain (SCG) are obtained to analyse the system in depth. Finally, Monte-Carlo Simulation is performed to verify the obtained results. The results manifest that the scenario with selection at each hop provides better secrecy performance than the scenario with selection at the last hop.

Oxya chinensis sinuosa (rice field grasshopper) is an edible insect with numerous health beneficial properties, traditionally being used to treat many ailments in Korea and other countries. O. chinensis sinuosa has been used from centuries, however, a little is known about the chemical functionality of its bioactive compounds. Therefore, this study examined the anti-inflammatory and cathepsin C inhibitory activities of N-acetyldopamine dimer (2R, 3S)-2-(3′,4′-dihydroxyphenyl)-3-acetylamino-7-(N-acetyl-2″-aminoethyl)-1,4-benzodioxane (DAB1) isolated from O. chinensis sinuosa. Results showed that DAB1 reduced the expression of pro-inflammatory mediator (iNOS, COX-2) and cytokines (TNF-α, IL-1β, and IL-6), and curtailed the nuclear translocation of NF-κB by inhibiting the phosphorylation of IκBα in lipopolysaccharide stimulated macrophages. Additionally, DAB1 inhibited cathepsin C activity at the cellular level, supported by in vitro assay (Ki, 71.56 ± 10.21 µM and Kis, 133.55 ± 18.2 µM). Moreover, combinatorial molecular simulation and binding free energy analysis suggested a significant stability and binding affinity of cathepsin C-DAB1 complex via formation of hydrogen bond and hydrophobic interactions with the catalytic residues (Gln228, Thr379, Asn380, and Hie381). Also, essential dynamics analysis showed DAB1 induced non-functional motions in cathepsin C structure. Collectively, DAB1 was concluded as anti-inflammatory and cathepsin C inhibiting agent and could be used in the drug development against respective diseases.

Excellent characteristics of multi-walled carbon nanotubes (MWCNTs), such as higher toughness and stiffness, enlarged strength, and high thermal conductivity, make them an attractive choice to improve surface characteristics and machining performance. In the current study, MWCNTs mixed with dielectric fluid in the wire electrical discharge machining (WEDM) process was used to enhance the machining performance of Nitinol shape memory alloy (SMA). Significance of WEDM machining variables such as current, pulse-on time (Ton), pulse-off time (Toff), and variation in powder concentration of MWCNTs are studied on material removal rate (MRR) and surface roughness (SR). The addition of MWCNTs substantially improves the machining performance by increasing MRR and simultaneously reducing the SR. Improvement in the MRR of 75.42% and SR of 19.15% is achieved with the use of MWCNTs at 1 g/L in comparison to the conventional WEDM process. An advanced parameterless TLBO algorithm is used for simultaneous optimization of multiple responses. An advanced parameterless TLBO algorithm is used to find the optimal solution of multiple responses. Single objective optimization result has yielded maximum MRR of 0.5262 g/min at a current of 5 A, Ton 110 μs, Toff 1 μs and MWCNTs amount of 1 g/L while minimum SR of 1.27 μm at a current of 1 A, Ton 1 μs, Toff 24 μs and MWCNTs amount of 1 g/L. MOTLBO algorithm is used for simultaneous optimization of MRR and SR. Lastly, the surface integrity of machined surfaces using a field emission scanning electron microscope (FESEM) is also studied to evaluate the effect of MWCNTs on recast layer thickness (RLT) and other surface defects. The incorporation of MWCNTs has shown a substantial reduction in RLT and other surface defects such as reduction in globules of debris, melted material deposition, micro-crack-free, and micro-pores-free surfaces.